Prenatal risk factors were examined in a group of children with moderate or severe cerebral palsy and severe mental retardation. Of 179 characteristics considered, 31 distinguished the severely handicapped group from controls. Only one of these significant risk factors, low birthweight of prior live born child, could be recognized at the time gravida registered for prenatal care. Three factors of labor and delivery (arrested progress of labor, lowest fetal heart rate in second stage of labor, and use of mid forceps distinguished affected children from controls. Twenty-five characteristics of the neonate were different, and most were markedly different, in children who were later severely handicapped as compared with controls. The greatest differences had to do with the occurrence of neonatal seizures, intracranial hemorrhage, neonatal neurological abnormality, respiratory difficulty, small size at birth, and low hemoglobin and hematocrit.